Review Paper Flavonoids and mechanisms of their anticancer action

Abstract: Numerous studies collected over the last decade indicate the beneficial health effects of flavonoids. The diseases that could be potentially cured with flavonoids include cancer, cardiovascular disease, diabetes, and neurodegenerative diseases. Flavonoids are natural compounds found in fruits, vegetables, tea, and plant leaves.They are present in every day diets. All flavonoids possess a similar core structure that consists of benzo-γ-pyrone with an attached benzene ring. The position at which the benzene ring is attached andthe presence of hydroxyl and methyl groups define the structural diversity of the flavonoids and a variety of the exerted biochemical effects. A π-conjugated structure of flavonoids along with a number of benzene ring substituents defines the active participation of flavonoids in redoxreactions and, as a result, the exhibition of antioxidant and pro-oxidant properties. While antioxidant properties appear to be favorable in maintaining good health, it is the pro-oxidant activity of flavonoids that forms the basis of numerous reactions leading to cancer preventive effects. The reactions of flavonoids with metal cations or peroxidases may result in the formation of polyphenol radicals that damage DNA and proteins, thus stimulating apoptosis. Flavonoids may also modify the activity of various enzymes, therefore modulating metabolism and affecting the dynamics of apoptotic cellular death. The aim of the present review is to summarize recent advances in understanding (1) the biochemical basis of the pro-oxidant properties of flavonoids brought about by metal cations and peroxidases, (2) the interactions of flavonoids with enzymes metabolizing xenobiotics, specifically carcinogens, and (3) the influence of flavonoids on the activity of drug efflux transporters. A special attention is devoted to the relationship between flavonoid structure and its potential pro-oxidant and anticancer activity